The tumor pericyte and its role in tumor angiogenesis
Final Report Abstract
Pericytes are supporting (mural) cells that associate with the abluminal, outer surface of the endothelial lining of blood vessels. Previous studies and clinical observations have suggested that pericytes help to stabilize the vessel wall and therefore play important roles in maintenance of a stable, mature and fully functional vasculature. Conversely, pericytes were frequently found to be loosely associated with tumor blood vessels, which is though to promote cancer cell intravasation and thereby metastasis. In the past, the functional characterization of pericytes was complicated because we lacked suitable transgenic tools the identification, isolation and targeting of these cells. Here, we have used recombineering techniques to generate Pdgfrb(BAC)-CreERT2 transgenic mice, which enable inducible gene targeting experiments in perivascular cells. Combining this line with fluorescent reporter animals revealed robust Cre activity in pericytes of the retinal vasculature as well as in tumor vessels. Experiments for live imaging, genetic fate mapping and the characterization of Notch signaling in tumor pericytes are currently ongoing. In addition, our work in the SPP has shed new light on the roles of ephrin-B2 and Notch in the regulation of VEGF-dependent and independent angiogenic growth, which may well stimulate the development of novel diagnostic and therapeutic strategies.
